Rebound of relapses after discontinuation of rituximab in a patient with MOG-IgG1 positive highly relapsing optic neuritis: a case report
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Myelin oligodendrocyte glycoprotein immunoglobulin G1 (MOG-IgG1)-associated disease is suggested as a separate disease entity distinct from multiple sclerosis and neuromyelitis optica spectrum disorder. Nonetheless, the optimal treatment regimen for preventing relapses in MOG-IgG1-associated disease remains unclear.
We describe the case of a 45-year-old man with MOG-IgG1-positive highly relapsing optic neuritis who had experienced 5 attacks over 21 months and had monocular blindness despite prednisolone and azathioprine therapy. He began treatment with rituximab, which reduced the rate of relapse markedly. Following discontinuation of rituximab, however, the patient experienced two successive optic neuritis attacks 2 and 4 months after B-lymphocyte restoration.
Highly relapsing MOG-IgG1-associated disease can be prevented with rituximab even when the MOG-IgG1 titers are relatively stationary. Discontinuation of rituximab and restoration of B-lymphocytes may be associated with the rebound of disease activity.
KeywordsMOG-IgG1 Optic neuritis Highly relapsing Rituximab
myelin oligodendrocyte glycoprotein
magnetic resonance imaging
neuromyelitis optica spectrum disorder
Myelin oligodendrocyte glycoprotein immunoglobulin G1 (MOG-IgG1)-associated disease is suggested as a separate disease entity distinct from multiple sclerosis and neuromyelitis optica spectrum disorder (NMOSD) with anti-aquaporin-4 IgG (AQP4-IgG); it has a predilection for the optic nerve rather than spinal cord, perineural enhancement extending to adjacent soft tissues on magnetic resonance imaging (MRI), and a less unfavorable prognosis than NMOSD . Recent studies with a sufficient number of patients and duration of follow-up have indicated that a considerable number of patients with MOG-IgG1 have relapsing attacks in the central nervous system followed by neurological deficits [2, 3]. Nonetheless, the optimal treatment regimen for preventing relapses in patients with MOG-IgG1-associated disease has only recently begun to be studied . Here, we describe a patient with highly relapsing optic neuritis (ON) associated with MOG-IgG1, whose ON attacks were relatively well-prevented with rituximab (RTX) treatment. However, the patient experienced rebounds of repeated ON attacks shortly after the restoration of B-cells following discontinuation of RTX.
Despite continued immunosuppressive treatment and due to the repeated ON attacks and the side effect of the steroid (chorioretinopathy), the patient was administered RTX (375 mg/m2, 3 weekly infusion for induction and 3 maintenance doses under CD19+ B-cell monitoring over 29 months). Although one mild ON attack (no light perception/1.2) occurred in the patient’s right eye during RTX treatment, the rate of relapse decreased markedly and the patient’s visual function was well-maintained. However, 32 months after the initiation of RTX treatment, we became unable to maintain RTX treatment due to insurance issues (denial for reimbursement). As a result, the treatment was switched to mycophenolate mofetil (250 mg twice per day) combined with oral prednisolone (5 mg every other day). The patient’s CD19+ B-lymphocyte level was restored to 2 and 4% at 9 and 11 months after the last RTX infusion, respectively. Subsequently, 2 more left ON attacks (hand movement/1.0 and hand movement/0.15) occurred within a one-month interval (Fig. 1-c and 1-D). The titer of MOG-IgG1 was measured by a geometric mean fluorescence (G-mean) ratio of the MOG-expressing cells bound to IgG1 using in-house flow cytometry. The G-mean ratio was calculated for each sera as followings: G-mean values of the patient’s sera / G-mean values of the healthy control. The titer was not associated with the continuation or cessation of the RTX treatment (Fig. 1-e).
Discussion and conclusions
Here, we describe the longitudinal clinical course and treatment response to RTX therapy in a patient with MOG-IgG1-positive highly relapsing ON. We found that 1) highly relapsing MOG-IgG1-associated disease can be prevented with RTX even when the MOG-IgG1 titers are relatively preserved, and 2) discontinuation of RTX in patients with this condition can cause rebound of disease activity with restoration of B-lymphocytes.
Initial reports regarding MOG-IgG1-associated disease indicated that it typically has a monophasic and benign disease course . However, recent multicenter studies have shown that a considerable proportion of patients have a relapsing course of disease, and some have significant neurological deficits [2, 3]. More recently, RTX was reported to reduce the rate of relapse in some cases of MOG-IgG1-associated disease . Nevertheless, the results of studies comparing the patient’s condition before vs. after the treatment should be interpreted with caution because the disease may have a naturally decreasing relapse rate in the later stages, as in NMOSD , and also the statistical phenomenon of regression towards the mean. In this regard, the present case, wherein we observed a restoration of B-lymphocytes and a subsequent rebound of relapses after discontinuation of RTX treatment, implies that long-term RTX maintenance therapy may be helpful in patients with highly relapsing MOG-IgG1-associated disease.
Despite initial treatment with azathioprine and prednisolone, the patient had a high relapse rate of 0.238/year (5 attacks over 21 months) and subsequent unilateral visual loss in the right eye. After initiating RTX treatment, his relapse rate markedly decreased to 0.031/year (1 attack over 32 months). However, the patient experienced 2 ON attacks over 4 months following cessation of RTX treatment and restoration of B-lymphocytes.
In summary, the case described here illustrates that RTX can be a good treatment option for preventing relapses in MOG-IgG1-associated disease. The treatment effect was observed despite the relatively unchanged MOG-IgG1 titers during the treatment period. Finally, cessation of RTX treatment and restoration of B-lymphocytes may be associated with the rebound of disease activity. RTX may serve as an effective treatment regimen in MOG-IgG1-associated disease, especially in patients with high relapse rates.
This work was supported by grant no. HI17C0335 and HI17C0789 from the Korea Health Industry Development Institute Research fund. The funders had no role in the design of the study, interpretation of data and in writing the manuscript. They had contributed to the data collection and analysis of AQP4-IgG and MOG-IgG1 antibodies.
Availability of data and materials
All data have been presented within the manuscript and in the form of images.
S-MK conceived of the study. S-JC and S-MK analyzed and interpreted the data, and involved in drafting and revising the manuscript. BK contributed to acquisition and analysis of the data, and involved in revising the manuscript critically. J-JS contributed to interpretation of the data, and involved in revising the manuscript critically. H-JL and S-JK made substantial contributions to interpretation of ophthalmological data and also involved in revising the manuscript critically; as a result, this manuscript came to have more intellectual content on ophthalmology. All listed authors have participated sufficiently in the work to take public responsibility for appropriate portions of the content, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Ethics approval and consent to participate
This study was approved by the ethics committee of Seoul National University Hospital (IRB no. 1005–023-317).
Consent for publication
Written informed consent was obtained from the patient for publication of this case report.
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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